Adiponectin Downregulates C‐Reactive Protein Synthesis and Secretion from Human Aortic Endothelial Cells: Evidence for a Adipose‐Vascular Loop

Abstract

C‐reactive protein (CRP), the prototypic marker of infammation, is a cardiovascular risk marker. Also, several lines of evidence point to a pro‐atherogenic role for CRP. We have previously shown that in addition to the liver, human aortic endothelial cells (HAEC) synthesize and secrete CRP. While CRP levels are increased in obesity, metabolic syndrome, diabetes and CAD, levels of the adipocyte‐derived hormone adiponectin are reduced in humans with these conditions. We tested the hypothesis that adiponectin reduces CRP synthesis and secretion in HAECs. Globular adiponectin dose dependently reduced CRP mRNA and protein from HAEC. Adiponectin treatment of HAEC significantly decreased phosphorylation of IKb and decreased NFKb binding activity. There was no effect of adiponectin on STAT or CEBP transcriptional activity. Globular adiponectin also activated AMP kinase resulting in decreased NFKb activity and decreased CRP mRNA and protein. These effects of adiponectin were mimicked by AICAR, an activator of AMPK and reversed by inhibition of AMPK. Globular adiponectin reduces CRP synthesis and secretion from HAEC via upregulation of AMP kinase and downregulation of NFKb. Similar findings were observed in rat primary hepatocytes. Thus, strategies aimed at upregulating adiponectin could attenuate the pro‐inflammatory state by decreasing CRP production.